The need for new and improved methods and agents for pain treatment is a significant ongoing concern in medicine. Acute pain, e.g. related to injury or disease, can be severe and have critical effects on patient recovery. An even greater concern is chronic pain, which affects a large proportion of the population, causing not only significant discomfort, but can result in low self-esteem, depression, anger, and can interfere with or completely prevent sufferer from typical daily activities.
While a number of studies have been done in this area, many mechanisms and pathways involved in pain sensation remain poorly understood. As in the case of the sensation of various stimuli, it has been suggested that pain sensation is related to altered neuronal excitability.
Ion cotransport has in some cases been thought to play a role in the processing of certain stimuli. For example, Howard et al. (28) have demonstrated that mice generated with a targeted deletion of the Slc12a6 gene, which encodes the KCC3 exporter, exhibit features of agenesis of the corpus callosum, including a locomotor deficit, peripheral neuropathy and a sensorimotor gating deficit. Sung et al. (29) report that in mice where there is a disruption of the Slc12a2 gene, which encodes the NKCC1 cotransporter, sensitivity to thermal stimulus is greatly reduced, compared to both wild-type and heterozygous (NKCC1+/−) mice.
There remains a need to better define the mechanisms involved in pain sensation to provide new strategies of therapeutic intervention in this regard.